Comparison of Kinetic and Dynamical Models of DNA-Protein Interaction and Facilitated Diffusion

Comparison of Kinetic and Dynamical Models of DNA-Protein Interaction and Facilitated Diffusion
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DOI:
10.1021/jp101151a
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发表时间:
2010-09-16
影响因子:
2.9
通讯作者:
Joyeux, Marc
Joyeux, Marc
中科院分区:
化学3区
文献类型:
--
作者:
Florescu, Ana-Maria;Joyeux, Marc

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长期以来,人们一直认为,由于易化扩散,即一维(沿沿着DNA滑动)和三维扩散的组合,蛋白质如转录因子可以以超过三维扩散极限几个数量级的速率在DNA序列中定位其靶。这种说法多年来一直得到几种质量作用动力学模型的支持,而我们最近提出的动力学模型(J.Chem.Phys.2009,130,015103)表明,由于易化扩散导致的靶向加速不可能很大。为了解决这一明显的矛盾,我们进行了额外的模拟,以比较我们的模型获得的结果与Klenin等人的动力学模型获得的结果。2006,96,018104)。在本文中,我们表明,这两个模型实际上相互支持,并同意在预测一个低效率的促进扩散。将这些结果外推到真实的系统甚至表明,与三维扩散相比,易化扩散必然会减慢靶向过程。
It has long been asserted that proteins such as transcription factors may locate their target in DNA sequences at rates that surpass by several orders of magnitude the three-dimensional diffusion limit thanks to facilitated diffusion, that is, the combination of one-dimensional (sliding along the DNA) and three-dimensional diffusion. This claim has been supported throughout the years by several mass action kinetic models, while the dynamical model we proposed recently (J. Chem. Phys. 2009, 130, 015103) suggests that acceleration of targeting due to facilitated diffusion cannot be large. In order to solve this apparent contradiction, we performed additional simulations to compare the results obtained with our model to those obtained with the kinetic model of Klenin et al. (Phys. Rev. Lett. 2006, 96, 018104). We show in this paper that the two models actually support each other and agree in predicting a low efficiency for facilitated diffusion. Extrapolation of these results to real systems even indicates that facilitated diffusion necessarily slows down the targeting process compared to three-dimensional diffusion.